Heat shock proteins (HSPs) are induced in response to a variety of cellular stresses, and appear to be critical for maintaining cellular homeostasis. Previously, we demonstrated that restraint or immobilization stress elicits the induction of HSP7O expression selectively in the adrenal gland and vasculature of intact rats. In both tissues this stress-induced HSP7O expression was found to be linked to the activation of the neuroendocrine stress response axes and to be attenuated with age. The adrenal response was found to be dependent on the hypothalamic-pituitary-adrenal axis and require adrenocorticotropic hormone (ACTH) while the vascular response appeared to be under alpha adrenergic control. Recent studies have focused on the molecular events controlling this response to restraint and the cause for its age-related decline. In the adrenal model we have shown that HSP7O induction is mediated by the heat shock transcription factor HSF1 and have shown that in Wistar rats HSF1 is activated to a DNA binding state by ACTH. Although properties of HSF1 and its activation in response to heat stress have been well studied in cultured cells, little information is available regarding the regulation of its activity in vivo. We have noted a number of differences in the properties of HSF1 in our in vivo model compared to that observed in heat stressed cells in vitro. These include the subcellular localization of HSF1 (which is mostly nuclear in the adrenal gland) and the differential mobility and DNA binding properties of the transcription factor in different rat strains. Despite differences in the nature of DNA binding HSF complexes in two different rat strains, the level DNA binding activity declines with age in both. In vascular tissue we have provided new evidence that in addition to adrenergic hormones, other agents capable of elevating blood pressure likewise induce HSP7O expression in the aorta. This suggests that mechanical stress associated with changes in blood pressure elicit the response. Our findings indicate that the activation of the heat shock response in vivo involves greater complexity than is observed in cultured cells in response to heat stress and suggest a broader role for HSPs in the physiologic response to stress than previously appreciated.